Among essential amino acids, tryptophan is unique for being the only one directly utilized in the synthesis of a neurotransmitter. While the body converts tryptophan to serotonin, it also uses the amino acid to make the hormone, melatonin, and the B vitamin, niacin. This rather special amino acid can, therefore, boost serotonin, melatonin and niacin levels. By doing these it improves mood, sleep and cognitive performance. Such effects make it effective in the management of premenstrual syndrome. But is their clinical evidence to support the use of tryptophan in the treatment of PMS? Is it a safer and better alternative to prescription antidepressants? Read on to find out.

Besides its function as one of the building blocks of proteins, tryptophan is also the precursor of a number of important non-protein compounds in the body. For example, this amino acid is required for the syntheses of serotonin, melatonin and niacin.

In the synthesis of serotonin, L-tryptophan is first converted to 5-hydroxytryptophan or 5HTP.

5HTP is also a popular dietary supplement and it is used for the same therapeutic purposes as L-tryptophan.

The 5HTP produced from this first reaction is then directly converted to serotonin. Serotonin is a neurotransmitter required for the regulation of mood, memory and sleep.

From serotonin, the synthesis continues on to melatonin, a neurohormone released from the pineal gland and closely involved in the sleep-wake cycle.

The metabolic pathway through which tryptophan is converted to the B vitamin, niacin (vitamin B3), is separate from the serotonin-melatonin pathway although it is a parallel pathway that competes for tryptophan too.

L-tryptophan is a unique amino acid because it is converted to serotonin and, therefore, an affordable and safer alternative to prescription drugs that act on the serotonergic pathway in the brain.

This means that L-tryptophan supplements are safe and effective alternatives for raising serotonin levels. And in this role, the amino acid produces an antidepressant effect just like SSRIs.

SSRIs or selective serotonin reuptake inhibitors are prescription antidepressants that act by blocking the clearance of serotonin from the synaptic junctions between neurons in the brain.

While they are effective, SSRIs do have their side effects. A number of studies have been conducted to compare L-tryptophan to SSRIs. The results of such studies show that the amino acid produces a comparable antidepressant effect to SSRIs and is safer too.

While SSRIs keep serotonin for longer at synaptic junction, L-tryptophan increases serotonin levels in the brain and, therefore, makes the neurotransmitter available for neurotransmission.

Therefore, while the efficacy of SSRIs depends on the availability of serotonin, L-tryptophan actually increases the availability of serotonin.

For mood changes and psychological disorders caused by the depletion of serotonin, L-tryptophan is the better treatment.

Studies have shown that most of the PMS symptoms involving emotion are caused by neurotransmitter imbalance in the central nervous system. Specifically, these symptoms can result from low levels of neurotransmitters such as serotonin and dopamine.

Because serotonin is important to mood, low levels of serotonin can be directly linked to the depression, irritability and mood changes experienced by women with PMS.

In addition, serotonin is important to the regulation of sleep. Low serotonin level may affect the onset and quality of sleep. In addition, low serotonin level also means low melatonin levels. The result is a significant disruption in the sleep-wake cycle.

While raising serotonin level is the major reason for taking L-tryptophan for PMS, the role of the amino acid as a precursor in the synthesis of niacin can also contribute to its efficacy in the management of the disorder.

L-tryptophan is converted to niacin in a 5-stage reaction that competes with the syntheses of serotonin and melatonin.

Unlike L-tryptophan, 5HTP cannot be converted to niacin because it is committed to serotonin and melatonin syntheses. Therefore, 5HTP cannot increase niacin levels in women with PMS.

For this reason, L-tryptophan is regarded as the better supplement for PMS.

But how does niacin help PMS? Like other B vitamins, niacin is essential to a long list of biochemical processes including those involved in cellular metabolism and DNA repair.

But more importantly, it is required for the production of steroid hormones such as estrogen and progesterone. Therefore, increasing niacin production can help prevent the sort of hormonal imbalance that promotes PMS.

In addition, L-tryptophan prevents niacin deficiency. This is important because niacin deficiency is one of the causes of low serotonin level.

This happens when the body diverts some tryptophan to niacin synthesis while starving the serotonin-melatonin pathway.

Therefore, L-tryptophan supplementation can saturate the niacin pathway and then progressively increase the levels of serotonin and melatonin.

L-tryptophan should not be used as the sole treatment for your PMS. Rather, it works best when combined with other supplements for PMS such as calcium, magnesium, vitamin D, vitamin E and vitamin B6.

In addition, the amino acid can also be combined with PMS herbal remedies such as chasteberry.

However, it should not be combined with St. John’s wort or other herbs that increase serotonin level or activity in the brain. Such combinations may lead to a potentially fatal condition known as serotonin syndrome.

For the same reason, L-tryptophan should not be combined with drugs that affect the serotonergic pathway.

Therefore, antidepressants, including SSRIs, as well as supplements such as 5HTP should be avoided while taking tryptophan.

Although there is no established dosage for the amino acid in the management of PMS, some health experts suggest taking 1,500 mg of L-tryptophan per day in combination with other supplements. Higher doses have been safely used in studies.

A small amount of carbohydrate is recommended to accompany L-tryptophan doses. Proteins should be avoided because they can actually lower the efficacy of L-tryptophan.

These proteins are guaranteed to release a number of amino acids to compete with L-tryptophan for absorption in the gut and for passage through the blood-brain barrier.

What is responsible for low serotonin level and activity in PMS? This is an important question because researchers believe that the changes in serotonergic pathway is responsible for most of the emotion-type symptoms of PMS.

To test this theory, researchers usually give L-tryptophan to women with PMS and those without the condition. As expected, L-tryptophan affects serotonin and neurohormone levels differently between these two groups of women.

This 2000 study published in the journal, Fertility and Sterility, is an example of the studies investigating this peculiar phenomenon.

For the study, the researchers monitored changes in neurotransmitter and hormone levels after challenging women with PMS and matched controls with intravenous L-tryptophan. Intravenous L-tryptophan was used to bypass intestinal absorption and produce quick results.

Following the L-tryptophan challenge, the researchers then measured blood levels of serotonin, cortisol and prolactin after 30, 50, 60, 70, 80 and 90 minutes.

The results of the study showed that the women with PMS produced far less serotonin from L-tryptophan during the luteal phase of their menstrual cycles when compared to the health controls free from the condition.

In addition, the researchers found that women with PMS have higher levels of circulating cortisol, an indicator of greater stress.

The researchers concluded that women with PMS handle tryptophan inefficiently. Therefore, these women were predisposed to PMS because the pathway responsible for serotonin synthesis was faulty.

In a 1991 paper published in the International Journal of Psychiatry in Medicine, the authors reviewed over 170 articles published on changes in serotonergic activities in women with PMS and PMDD (premenstrual dysphoric disorder, a more severe form of PMS).

From the evidence gathered, the researchers confirmed that response to serotonin was altered during the latter part of the luteal phase of the menstrual cycle.

In addition, they found that some functions of the serotonergic pathway were altered for the entire duration of the menstrual cycle.

The researchers attributed these changes to the influences of sex hormones such as estrogen.

Lastly, they concluded that agents that increased serotonin level and activities in the brain will help reduce the symptoms of PMS. Therefore, it is possible to overcome this impairment in serotonergic pathway with high dose L-tryptophan supplementation.

A 1991 study published in the journal, Psychological Medicine, built on the mounting evidences that serotonin response was modified in women with PMS.

In this study, the researchers also challenged women (with and without PMS depression) with intravenous L-tryptophan.

The outcomes of the study showed that serotonin was not the only brain chemical affected by PMS.

The results showed that response to the tryptophan challenge also affected the neuroendocrine system and produced smaller changes in cortisol and growth hormone levels in women suffering from PMS depression.

In their conclusion, the researchers believe that the interaction between the neurotransmitter and neuroendocrine changes leave women with PMS vulnerable to depression during the luteal phase of the menstrual cycle.

To determine if tryptophan level is directly tied to serotonin level in the brain, a group of researchers investigated the effect of acute tryptophan depletion on the synthesis of serotonin in the brain.

For the 1994 study published in the Journal of Affective Disorders, the researchers recruited 16 women with PMS and reduced their tryptophan intakes for the duration of the study.

The tryptophan depletion resulted in the worsening of PMS symptoms especially irritability.

The researchers also noted that the severity of PMS symptoms were positively correlated with depletion of tryptophan relative to other amino acids.

Since tryptophan competes with certain amino acids for the same transport mechanism to cross the blood-brain barrier, some experts believe that tryptophan depletion may be caused by this competition with other amino acids.

In addition, such competition for transport proteins may reduce the efficacy of tryptophan supplementation.

However, this 1991 study published in the American Journal of Obstetrics and Gynecology found that the competition between amino acids was not enough to cause tryptophan depletion.

For the study, the researcher measured the plasma levels of tryptophan and the neutral amino acids sharing the same transport proteins with it. Their results showed that there was no difference in the ratio of tryptophan to competing amino acids between women with PMS and those without.

In addition, they found that this ratio remained unchanged all through the different phases of the menstrual cycle.

Therefore, they concluded that it is unlikely that the competition between amino acids for tryptophan transport mechanism was responsible for PMS symptoms.

Can PMS symptoms be improved by taking L-tryptophan? This 1985 case study published in the journal, Psychiatric Forum, suggested so.

The article discussed the case of a 35-year old woman with a 20-year history of PMS. When placed on 1,000 mg of L-tryptophan given orally for 5 times every day, the patient reported relief in anxiety and depression.

This subjective improvement was also confirmed by objective results from the Brief Psychiatric Rating Scale.

In addition, the woman experienced improvements in sleep disturbance and headache.

The researchers attributed this efficacy of L-tryptophan to its ability to increase serotonin level in the brain.

A 1999 study published in the journal, Biological Psychiatry, detailed a placebo-controlled, double-blind clinical trial of L-tryptophan in the treatment of PMS and PMDD.

For this study, the researchers recruited 71 women with PMDD and randomly assigned 37 of them to receive 6 g of L-tryptophan per day while the rest were placed on placebo. The treatment period covered 17 days and extended from the beginning of ovulation to the 3rd day of menstruation for 3 consecutive menstrual cycles.

The results of the study showed that L-tryptophan was significantly better than placebo in the treatment of PMDD.

The researchers attributed this improvement in symptoms to a boost in serotonin level during the luteal phase of the menstrual cycle.

Therefore, this study confirms that L-tryptophan supplementation is effective for women with PMS and even the more severe PMDD. It also demonstrates the safety of this high-dose L-tryptophan supplementation when used as the sole therapy for PMS.